Progressive Systemic Sclerosis ACMS Dept of Medicine 2010 Batch VIII Term
Progressive Systemic Sclerosis
ACMS Dept of Medicine 2010 Batch VIII Term
PSS: Definition
• Systemic sclerosis (previously called 'scleroderma') is a generalised disorder of connective tissue affecting-
• The skin • Internal organs and • Vasculature.
PSS: Hallmark
The clinical hallmark is the presence of • Sclerodactyly in combination with • Raynaud's phenomenon or • Digital ischaemia
PSS: Epidemiology
• The peak age of onset is in 4th & 5th decades • Overall prevalence is 10-20 per 100 000 • 4:1 female: male ratio
PSS: Classification
It is subdivided into • Diffuse cutaneous systemic sclerosis (DCSS)• Limited cutaneous systemic sclerosis (LCSS)
• Many patients with LCSS have features which are phenotypically grouped into the 'CREST' syndrome (calcinosis, Raynaud's, oesophageal involvement, sclerodactyly, telangiectasia).
PSS: ClassificationIt is subdivided into • Diffuse cutaneous systemic sclerosis (DCSS)• Limited cutaneous systemic sclerosis (LCSS)
• Many patients with LCSS have features which are phenotypically grouped into the 'CREST' syndrome (calcinosis, Raynaud's, oesophageal involvement, sclerodactyly, telangiectasia).
CREST syndrome
Systemic Manifestations
PSS: Etiopathology
• Unknown, • No consistent genetic, geographical or racial
associations. • Environmental factors are important in
isolated cases that result from exposure to – silica dust, – vinyl chloride, –hypoxy resins and – trichloroethylene.
PSS: Etiopathology
Early in the disease there is • Skin infiltration by T lymphocytes• Abnormal fibroblast activation
• That leads to increased production of extracellular matrix in the dermis, primarily type I collagen.
• This results in symmetrical thickening, tightening and induration of the skin (sclerodactyly).
PSS: Etiopathology
Early in the disease there is –Skin infiltration by T lymphocytes and –Abnormal fibroblast activation
• In addition to skin changes there is arterial and arteriolar narrowing due to intimal proliferation and vessel wall inflammation.
• Endothelial injury causes release of vasoconstrictors and platelet activation, resulting in further ischaemia.
PSS Clinical Features and Diagnoais
• Systemic sclerosis is predominantly a clinical diagnosis based on the presence of sclerodactyly.
• Most patients are ANA-positive, and • Approximately 30% of patients with diffuse
disease and • 60% with limited disease have antibodies to
topoisomerase 1 and centromere respectively.
• Cutaneous changes Raynaud's phenomenon is universal and may precede other clinical features.
• Systemic sclerosis. Hands showing tight shiny skin, sclerodactyly, flexion contractures of the fingers and thickening of the left middle finger extensor tendon sheath
PSS: Skin Disease
• The initial phase of skin disease is characterised by non-pitting oedema of the fingers and flexor tendon sheaths.
• Subsequently, the skin becomes shiny and taut, and distal skin creases disappear.
• There is usually erythema and tortuous dilatation of capillary loops in the nail-fold bed, readily visible with an ophthalmoscope.
• The face and neck are usually involved next, with thinning of the lips and radial furrowing. In some patients skin thickening stops at this stage.
PSS: Skin Disease• Skin involvement restricted to sites distal to
the elbow or knee (apart from the face) is classified as 'limited cutaneous disease' or CREST syndrome.
• Involvement proximal to the knee and elbow and on the trunk is classified as 'diffuse cutaneous disease'.
PSS: Skin DiseaseIn extremities- • Intimal fibrosis and vessel wall inflammation may
combine to cause critical tissue ischaemia, skin ulceration on pressure points
• Localised areas of infarction and • Pulp atrophy at the fingertips.
PSS: Musculoskeletal features
• Arthralgia, morning stiffness and flexor tenosynovitis are common.
• Restricted hand function is due to skin rather than joint disease and erosive arthropathy is uncommon.
• Muscle weakness and wasting are usually due to myositis.
PSS: GI FEATURES
• Gut involvement is common. • Smooth muscle atrophy and fibrosis in
the lower two-thirds of the oesophagus lead to acid reflux with erosive oesophagitis.
• Since this may progress to further fibrosis, adequate treatment of reflux (proton pump inhibitors) is important.
• Dysphagia and odynophagia (painful dysphagia) may also occur.
PSS: GI FEATURES• Involvement of the stomach causes early satiety
and occasionally outlet obstruction. • Recurrent occult upper GI bleeding may indicate
a 'watermelon stomach' (antral vascular ectasia), which occurs in up to 20% of patients.
• Small intestine involvement may lead to malabsorption, bacterial overgrowth and intermittent bloating, pain or constipation.
• Dilatation of large or small bowel due to autonomic neuropathy may cause pseudo-obstruction.
Watermelon Stomach
PSS: Cardiorespiratory features • Pulmonary involvement is a major cause of
morbidity and mortality. • Fibrosing alveolitis mainly affects pts with diffuse
disease, esp those with antibodies to topoisomerase 1.
• Pulmonary hypertension is a long-standing complication. It is 6X more prevalent in limited than diffuse disease.
• The clinical features are rapidly progressive dyspnoea (more than ILD), RHF and angina with-
• often rapidly progressing digital ischaemia.
PSS: Cardiorespiratory features Treatment strategies include • Vasodilators • Continuous infusions of epoprostenol • The oral endothelin 1 antagonist bosentan and• Heart-lung transplantation.
PSS: Renal features
• Main cause of death is hypertensive renal crisis (rapidly developing malignant hypertension and renal failure).
• Treatment is by ACE inhibition even in presence of renal impairment.
• Hypertensive renal crisis is more likely in patients with diffuse rather than limited disease.
• It is also more prevalent in patients with topoisomerase 1 antibodies.
• Clinicians use prophylactic ACE Is for diffuse disease to prevent this manifestation.
PSS: Management and prognosis Five-year survival is approx70%. Risk factors for a poor prognosis include • Older age • Diffuse skin disease • Proteinuria • High ESR • A low gas transfer factor for carbon monoxide
(TLCO) and • Pulmonary hypertension
PSS: Management and prognosis • Self-management to maintain core body
temperature and avoid peripheral cold exposure is important.
• Infection of ulcerated skin should be treated with prompt antibiotic therapy.
• Antibiotics penetrate poorly into the skin lesions of systemic sclerosis and therefore need to be given at higher dose for longer periods (e.g. flucloxacillin 500 mg 6-hourly for 14 days).
PSS: Management and prognosis • Calcium antagonists (e.g. nifedipine,
amlodipine) or angiotensin II receptor antagonists (e.g. valsartan) may be effective for Raynaud's symptoms.
• For severe digital ischaemia, intermittent infusions of epoprostenol may be helpful.
PSS: Management and prognosis • Corticosteroids and cytotoxic drugs are
indicated in patients with myositis or alveolitis.
• No agent has been shown to arrest or improve skin changes.